{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:49:38Z","timestamp":1781632178318,"version":"3.54.5"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T00:00:00Z","timestamp":1578355200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T00:00:00Z","timestamp":1578355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hepatol Int"],"published-print":{"date-parts":[[2020,5]]},"DOI":"10.1007\/s12072-019-10010-3","type":"journal-article","created":{"date-parts":[[2020,1,7]],"date-time":"2020-01-07T16:27:02Z","timestamp":1578414422000},"page":"385-398","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Adverse outcomes of proton pump inhibitors in chronic liver disease: a systematic review and meta-analysis"],"prefix":"10.1007","volume":"14","author":[{"given":"Junna","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangpeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianglong","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingtao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiang","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,7]]},"reference":[{"key":"10010_CR1","doi-asserted-by":"publisher","first-page":"1856","DOI":"10.1001\/jamainternmed.2014.2900","volume":"174","author":"ME Johansen","year":"2014","unstructured":"Johansen ME, Huerta TR, Richardson CR. National use of proton pump inhibitors from 2007 to 2011. JAMA Intern Med 2014;174:1856\u20131588","journal-title":"JAMA Intern Med"},{"key":"10010_CR2","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s12916-017-0804-x","volume":"15","author":"R Yadlapati","year":"2017","unstructured":"Yadlapati R, Kahrilas PJ. When is proton pump inhibitor use appropriate? BMC Med 2017;15:36","journal-title":"BMC Med"},{"key":"10010_CR3","doi-asserted-by":"publisher","first-page":"e56060","DOI":"10.1371\/journal.pone.0056060","volume":"8","author":"S Rotman","year":"2013","unstructured":"Rotman S, Bishoop T. Proton pump inhibitor use in the US ambulatory setting, 2002\u20132009. PLoS One 2013;8:e56060","journal-title":"PLoS One"},{"key":"10010_CR4","doi-asserted-by":"publisher","first-page":"182","DOI":"10.5056\/jnm18001","volume":"24","author":"Y Kinoshita","year":"2018","unstructured":"Kinoshita Y, Ishimura N, Ishihara S. Advantages and disadvantages of long-term proton pump inhibitor use. J Neurogastroenterol Motil 2018;24:182\u2013196","journal-title":"J Neurogastroenterol Motil"},{"key":"10010_CR5","doi-asserted-by":"publisher","first-page":"175628481983451","DOI":"10.1177\/1756284819834511","volume":"12","author":"KS Cheung","year":"2019","unstructured":"Cheung KS, Leung WK. Long-term use of proton-pump inhibitors and risk of gastric cancer: a review of the current evidence. Therap Adv Gastroenterol 2019;12:1756284819834511","journal-title":"Therap Adv Gastroenterol"},{"key":"10010_CR6","first-page":"CR468","volume":"14","author":"NC Chavez-Tapia","year":"2008","unstructured":"Chavez-Tapia NC, Tellez-Avila FI, Garcia-Leiva J, Valdovinos MA. Use and overuse of proton pump inhibitors in cirrhotic patients. Med Sci Monit 2008;14:CR468\u2013CR472","journal-title":"Med Sci Monit"},{"key":"10010_CR7","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1111\/bcp.13615","volume":"84","author":"RA Weersink","year":"2018","unstructured":"Weersink RA, Bouma M, Burger DM, Drenth JP, Harkes-Idzinga SF, Hunfeld NG, et al. Safe use of proton pump inhibitors in patients with cirrhosis. Br J Clin Pharmacol 2018;84:1806\u20131820","journal-title":"Br J Clin Pharmacol"},{"key":"10010_CR8","doi-asserted-by":"publisher","first-page":"b2700","DOI":"10.1136\/bmj.b2700","volume":"339","author":"A Liberati","year":"2009","unstructured":"Liberati A, Altman DG, Tetzlaff J, Mulrow C, G\u00f8tzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700","journal-title":"BMJ"},{"key":"10010_CR9","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s10654-010-9491-z","volume":"25","author":"A Stang","year":"2010","unstructured":"Stang A. Critical evaluation of the Newcastle\u2013Ottawa scale for the assessment of the quality of non randomized studies in meta-analyses. Eur J Epidemiol 2010;25:603\u2013605","journal-title":"Eur J Epidemiol"},{"key":"10010_CR10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.cct.2006.04.004","volume":"28","author":"R DerSimonian","year":"2007","unstructured":"DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 2007;28:105\u2013114","journal-title":"Contemp Clin Trials"},{"key":"10010_CR11","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","volume":"7","author":"R DerSimonian","year":"1986","unstructured":"DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177\u2013188","journal-title":"Control Clin Trials"},{"key":"10010_CR12","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1002\/sim.1186","volume":"21","author":"JP Higgins","year":"2002","unstructured":"Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539\u20131558","journal-title":"Stat Med"},{"key":"10010_CR13","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1136\/bmj.315.7109.629","volume":"315","author":"M Egger","year":"1997","unstructured":"Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629\u2013634","journal-title":"BMJ"},{"key":"10010_CR14","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1002\/hep.20593","volume":"41","author":"NJ Shaheen","year":"2005","unstructured":"Shaheen NJ, Stuart E, Schmitz SM, Mitchell KL, Fried MW, Zacks S, et al. Pantoprazole reduces the size of post banding ulcers after variceal band ligation: a randomized, controlled trial. Hepatology 2005;41:588\u2013594","journal-title":"Hepatology"},{"key":"10010_CR15","doi-asserted-by":"publisher","first-page":"866","DOI":"10.1111\/apt.12045","volume":"36","author":"JS Bajaj","year":"2012","unstructured":"Bajaj JS, Ratliff SM, Heuman DM, Lapane KL. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Aliment Pharmacol Ther 2012;36:866\u2013874","journal-title":"Aliment Pharmacol Ther"},{"key":"10010_CR16","doi-asserted-by":"publisher","first-page":"f5416","DOI":"10.1136\/bmj.f5416","volume":"347","author":"BT Bateman","year":"2013","unstructured":"Bateman BT, Bykov K, Choudhry NK, Schneeweiss S, Gagne JJ, Polinski JM, et al. Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ 2013;347:f5416","journal-title":"BMJ"},{"key":"10010_CR17","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s00535-017-1371-9","volume":"53","author":"T Su","year":"2018","unstructured":"Su T, Lai S, Lee A, He X, Chen S. Meta-analysis: proton pump inhibitors moderately increase the risk of small intestinal bacterial overgrowth. J Gastroenterol 2018;53:27\u201336","journal-title":"J Gastroenterol"},{"key":"10010_CR18","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s12072-018-9898-2","volume":"12","author":"R Maslennikov","year":"2018","unstructured":"Maslennikov R, Pavlov C, Ivashkin V. Small intestinal bacterial overgrowth in cirrhosis: systematic review and meta-analysis. Hepatol Int 2018;12:567\u2013576","journal-title":"Hepatol Int"},{"key":"10010_CR19","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1111\/j.1365-2362.1989.tb00246.x","volume":"19","author":"A Masclee","year":"1989","unstructured":"Masclee A, Tangerman A, van Schaik A, van der Hoek EW, van Tongeran JHM. Unconjugated serum bile acid as a marker of small intestinal bacterial overgrowth. Eur J Clin Invest 1989;19:384\u2013389","journal-title":"Eur J Clin Invest"},{"key":"10010_CR20","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.jhep.2007.06.001","volume":"47","author":"PLM Jansen","year":"2007","unstructured":"Jansen PLM. Endogenous bile acids as carcinogens. J Hepatol 2007;47:434\u2013435","journal-title":"J Hepatol"},{"key":"10010_CR21","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1136\/gutjnl-2015-310376","volume":"65","author":"F Imhann","year":"2016","unstructured":"Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L, et al. Proton pump inhibitors affect the gut microbiome. Gut 2016;65:740\u2013748","journal-title":"Gut"},{"key":"10010_CR22","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1038\/nrgastro.2017.117","volume":"14","author":"P Malfertheiner","year":"2017","unstructured":"Malfertheiner P, Kandulski A, Venerito M. Proton-pump inhibitors: understanding the complications and risks. Nat Rev Gastroenterol Hepatol 2017;14:697","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10010_CR23","first-page":"533","volume":"20","author":"K Cohen-Hagai","year":"2018","unstructured":"Cohen-Hagai K, Feldman D, Turani-Feldman T, Hadary R, Lotan S, Kitay-Cohen Y. Magnesium deficiency and minimal hepatic encephalopathy among patients with compensated liver cirrhosis. Israel Med Assoc J IMAJ 2018;20:533\u2013538","journal-title":"Israel Med Assoc J IMAJ"},{"key":"10010_CR24","doi-asserted-by":"publisher","first-page":"301","DOI":"10.4103\/1319-3767.101123","volume":"18","author":"W Bleibel","year":"2012","unstructured":"Bleibel W, Al-Osaimi AMS. Hepatic encephalopathy. Saudi J Gastroenterol 2012;18:301\u2013309","journal-title":"Saudi J Gastroenterol"},{"key":"10010_CR25","doi-asserted-by":"publisher","first-page":"e110503","DOI":"10.1371\/journal.pone.0110503","volume":"9","author":"M Mandorfer","year":"2014","unstructured":"Mandorfer M, Bota S, Schwabl P, Bucsics T, Pfisterer N, Summereder C, et al. Proton pump inhibitor intake neither predisposes to spontaneous bacterial peritonitis or other infections nor increases mortality in patients with cirrhosis and ascites. PLoS One 2014;9:e110503","journal-title":"PLoS One"},{"key":"10010_CR26","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1002\/lt.24794","volume":"23","author":"C Moctezuma-Velazquez","year":"2017","unstructured":"Moctezuma-Velazquez C, Kalainy S, Abraldes JG. Beta-blockers in patients with advanced liver disease: has the dust settled? Liver Transpl 2017;23:1058\u20131069","journal-title":"Liver Transpl"},{"key":"10010_CR27","doi-asserted-by":"publisher","first-page":"e0162987","DOI":"10.1371\/journal.pone.0162987","volume":"11","author":"TH Hung","year":"2016","unstructured":"Hung TH, Lay CJ, Tseng CW, Tsai CC, Tsai CC. The effect of renal function impairment on the mortality of cirrhotic patients: a nationwide population-based 3-year follow-up study. PLoS One 2016;11:e0162987","journal-title":"PLoS One"},{"key":"10010_CR28","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1053\/j.gastro.2019.05.056","volume":"157","author":"P Moayyedi","year":"2019","unstructured":"Moayyedi P, Eikelboom JW, Bosch J, Connolly SJ, Dyal L, Shestakovska O, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019;157:682\u2013691.e2","journal-title":"Gastroenterology"}],"container-title":["Hepatology International"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-019-10010-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s12072-019-10010-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s12072-019-10010-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,6]],"date-time":"2021-01-06T01:36:51Z","timestamp":1609897011000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s12072-019-10010-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,7]]},"references-count":28,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10010"],"URL":"https:\/\/doi.org\/10.1007\/s12072-019-10010-3","relation":{},"ISSN":["1936-0533","1936-0541"],"issn-type":[{"value":"1936-0533","type":"print"},{"value":"1936-0541","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,7]]},"assertion":[{"value":"6 September 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Junna Wang, Yangpeng Wu, Qiu Bi, Xianglong Zheng, Jingtao Zhang, and Wenxiang Huang declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All procedures were in accordance with the ethical standards of institutional and national committee on human experimentation and with the 1964 Helsinki Declaration. There was no interaction with patients directly, as we acquired data from already published articles.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}